Search results for: biological pathway

Authors: Maryam Zahedi Fard, Nazia Abdul Majid, Hapipah Mohd Ali, Mahmood Ameen Abdulla

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New quinazoline schiff base 3-(5-bromo-2-hydroxy-3-methoxybenzylideneamino)-2-(5-bromo-2-hydroxy-3-methoxyphenyl)-2,3-dihydroquinazolin-4(1H)-one was investigated for anticancer activity against MCF-7 human breast cancer cell line with involved mechanism of apoptosis. The compound demonstrated a remarkable antiproliferative effect, with an IC50 value of 3.41 ± 0.34, after 72 hours of treatment. Morphological apoptotic features in treated MCF-7 cells were observed by AO/PI staining. Furthermore, treated MCF-7 cells subjected to apoptosis death, as exhibited by perturbation of mitochondrial membrane potential and cytochrome c release as well as increase in ROS generation. We also found activation of caspases 3/7 and -9. Moreover, acute toxicity test demonstrated the nontoxic nature of the compound in mice. Our results showed the selected compound significantly induce apoptosis in MCF-7 cells via intrinsic pathway, which might be considered as a potent candidate for further in vivo and clinical breast cancer studies.

Keywords: antiproliferative effect, MCF-7 human breast cancer cell line, apoptosis, caspases

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Authors: Ruqia Nazir, Robin Perutz

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Collision-induced dissociation (CID) can be used to study the intrinsic properties of ions in the gas phase.1 Decay pathways of transition metal difluoride complexes of titanium, zirconium, hafnium, and ruthenium were studied by CID in an ESI-Ion trap mass spectrometer. Furthermore, the decay pathways of multiply charged anions (MCAs) of titanium and zirconium were also studied. The CID results are illustrated by the behaviour of (Cp*)₂TiF₂, which initially forms the ions [M-F-]⁺, [M+Na]⁺, and [M+K]⁺. The [(Cp*₂)TiF⁺ ion decays on resonant excitation to lose HF forming [Cp*(C₅Me₄CH₂)Ti]⁺ (Figure). The other major ion, [(Cp*)₂TiF₂+Na]⁺, decays on resonant excitation with production of [(Cp*)₂TiF₂]⁺ and [C₅Me₄CH₂]⁺. We also report the behaviour of Cp₂MF₂ (M = Zr, Hf) and Ru(PMe₃)₄F₂. The decay pathway of the multiply charged anions (MCAs), notably TiF₆²⁻ and ZrF₆²⁻ was concluded to be ionic fragmentation with loss of F⁻ rather than electron detachment.

Keywords: collision induced dissociation, transition metal difluoride comolexes, multiply charged anions, mass spectrometry

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Authors: Lorenzo Maiorino, Fabio Fortuna, Giovanni Panebianco, Marco Sanzari, Gabriella Arcese, Valerio Maria Paolozzi

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It is well known that sport is a factor of social cohesion and the breaking down of barriers between people. From this point of view, the aim is to demonstrate how, through the (re)generation of sustainable structures, it is possible to give life to a new social, cultural, and economic pathway, where possible, in peripheral areas with problems of abandonment and degradation. The aim of this paper is, therefore, to study realities such as European programs and funds and to highlight the ways in which planning can be used to respond to critical issues such as urban decay, abandonment, and the mitigation of social differences. For this reason, the analysis will be carried out through the Multiannual Financial Framework (MFF) package, the Next Generation EU, the Recovery and Resilience Facility (RRF), the Cohesion Fund, the European Social Fund, and other managed funds. The procedure will rely on sources and data of unquestionable origin, and the relation to the object of study in question will be highlighted. The project lends itself to be ambitious and exploring a further aspect of the sports theme, which, as we know, is one of the foundations for a healthy society.

Keywords: sport, social inclusion, urban regeneration, sports facilities, European funds

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Authors: Thomas Schalow

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This paper posits the need to take a cross-cultural approach to communication with non-human cultures and intelligences in order to meet the following three imminent contingencies: communicating with sentient biological intelligences, communicating with extraterrestrial intelligences, and communicating with artificial super-intelligences. The paper begins with a discussion of how intelligence emerges. It disputes some common assumptions we maintain about consciousness, intention, and language. The paper next explores cross-cultural communication among humans, including non-sapiens species. The next argument made is that we need to become much more serious about communicating with the non-human, intelligent life forms that already exist around us here on Earth. There is an urgent need to broaden our definition of communication and reach out to the other sentient life forms that inhabit our world. The paper next examines the science and philosophy behind CETI (communication with extraterrestrial intelligences) and how it has proven useful, even in the absence of contact with alien life. However, CETI’s assumptions and methodology need to be revised and based on the cross-cultural approach to communication proposed in this paper if we are truly serious about finding and communicating with life beyond Earth. The final theme explored in this paper is communication with non-biological super-intelligences using a cross-cultural communication approach. This will present a serious challenge for humanity, as we have never been truly compelled to converse with other species, and our failure to seriously consider such intercourse has left us largely unprepared to deal with communication in a future that will be mediated and controlled by computer algorithms. Fortunately, our experience dealing with other human cultures can provide us with a framework for this communication. The basic assumptions behind intercultural communication can be applied to the many types of communication envisioned in this paper if we are willing to recognize that we are in fact dealing with other cultures when we interact with other species, alien life, and artificial super-intelligence. The ideas considered in this paper will require a new mindset for humanity, but a new disposition will prepare us to face the challenges posed by a future dominated by artificial intelligence.

Keywords: artificial intelligence, CETI, communication, culture, language

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Authors: Ihtisham Bukhari

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In the current study, we enrolled a 46, XY phenotypically female patient bearing testes in her inguinal canal. DNA sequencing of the AR gene detected a missense mutation C.1715A > G (p. Y572C) in exon 2 which is already known to cause Complete androgen insensitivity syndrome (CAIS). We further studied the effects of this mutation on the testicular histopathology of the patient. No spermatocytes were seen in the surface spreading of testicular tissues while H&E staining showed that seminiferous tubules predominantly have only Sertoli cells. To confirm this meiotic failure is likely due to the current AR mutation we performed mRNA expression of genes associated with AR pathway, expression and location of the associated proteins in testicular tissues. Western blot and real-time PCR data showed that the patient had high levels of expression of AMH, SOX9, and INNB in testis. Tubules were stained with SOX9 and AMH which revealed Sertoli cell maturation arrest. Therefore, we suggest that AR mutation enhances AMH expression which ultimately leads to failure in the maturation of Sertoli cells and failure in spermatogenesis.

Keywords: androgen receptor, spermatogenesis, infertility, Sertoli cell only syndrome

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Authors: Yashfeen Khan, Anees Ahmad

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In the last few decades, nano-composites have been the topic of interest. Presently, the modern era enlightens the synthesis of hybrid nano-composites over their individual counterparts because of higher application potentials and synergism. Recently, CNT hybrids have demonstrated their pronounced capability as effective sorbents for the removal of heavy metal ions (the root trouble) and organic contaminants due to their high specific surface area, enhanced reactivity, and sequestration characteristics. The present abstract discusses removal efficiencies of organic, inorganic pollutants through CNT/PANI/ composites. It also represents the widespread applications of CNT like monitoring biological systems, biosensors, as heat resources for treating cancer, fire retardant applications of polymer/CNT composites etc. And considering the same, this article aims to brief the scenario of CNT-PANI nano-composites.

Keywords: biosensors, CNT, hybrids, polyaniline, synergism

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Authors: Luke Andrighetto, Paul G. Stevenson, Luke C. Henderson, Jim Pearson, Xavier A. Conlan

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As pseudoephedrine, a common ingredient in cold and flu medications is closely monitored and restricted in Australia, alternative methods of accessing it are of interest. The impurities and by-products of every reaction step of pseudoephedrine/ephedrine and methamphetamine synthesis have been mapped in order to develop a chemical fingerprint based on synthetic route. Likewise, seized methamphetamine contains a combination of different cutting agents and starting materials. Therefore, in-silico optimised two-dimensional HPLC with DryLab® and OpenMS® software has been used to efficiently separate complex seizure samples. An excellent match between simulated and real separations was observed. Targeted separation of model compounds was completed with significantly reduced method development time. This study produced a two-dimensional separation regime that offers unprecedented separation power (separation space) while maintaining a rapid analysis time that is faster than those previously reported for gas chromatography, single dimension high performance liquid chromatography or capillary electrophoresis.

Keywords: chemical fingerprint, ephedrine, methamphetamine, two-dimensional HPLC

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Authors: Fazilet Özlem Çekiç, Seyda Yılmaz

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Salinity and drought are important environmental problems in the world and have negative effects on plant metabolism. Gamma-aminobutyric acid (GABA), four-carbon non-protein amino acid, is a significant component of the free amino acid pool. GABA is widely distributed in prokaryotic and eukaryotic organisms. Environmental stress factors increase GABA accumulation in plants. Our aim was to evaluate the effect of gibberellic acid (GA) on GABA metabolism system during drought and salt stress factors in Phaseolus vulgaris L. plants. GABA, Glutamate dehydrogenase (GDH) activity, chlorophyll, and lipid peroxidation (MDA) analyses were determined. According to our results we can suggest that GA play a role in GABA metabolism during salt and drought stresses in bean plants. Also GABA shunt is an important metabolic pathway and key signaling allowing to adapt to drought and salt stresses.

Keywords: gibberellic acid, GABA, Phaseolus vulgaris L., salinity, drought

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Authors: Belahmadi M. S. O., Abdessemed A., Benchiheub M., Doukali H., Kaid Kasbah K. M.

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The aim of this study is to evaluate the quality of leachate generated by the Batna landfill site, and to verify the performance of various advanced oxidation processes, in particular the Fenton and Photo-Fenton systems combined with biological treatment to eliminate the recalcitrant organic matter contained in this effluent, and to preserve reverse osmosis membranes used for leachate treatment. The average values obtained are compared with national and international discharge standards. The results of physico-chemical analyses show that the leachate has an alkaline pH =8.26 and a high organic load with a low oxygen content. Mineral pollution is represented by high conductivity (38.3 mS/cm), high Kjeldahl nitrogen content (1266.504 mg/L) and ammoniacal nitrogen (1098.384 mg/L). The average pollution indicator parameters measured were: BOD5 = 1483.333 mg O2 /L, COD = 99790.244 mg O 2/L, TOC = 22400 mg C/L. These parameters exceed Algerian standards. Hence, there is a necessity to treat this effluent before discharging it into the environment. A comparative study was carried out to estimate the efficiency of two oxidation processes. Under optimum reaction conditions, TOC removal efficiencies of 63.43% and 73.4% were achieved for the Fenton and Photo-Fenton processes, respectively. COD removal rates estimated at 88% and 99.5% for the Fenton and Photo- Fenton processes, respectively. In addition, the Photo-Fenton + bacteria + micro- algae hybrid treatment gave removal efficiencies of around 92.24% for TOC and 99.9% for COD; -0.5 for AOS and 0.01 for CN. The results obtained during this study showed that a hybrid approach combining the PhotoFenton process and biological treatment appears to be a highly effective alternative for achieving satisfactory treatment, which aimed at exploiting the advantages of this method in terms of organic pollutant removal.

Keywords: leachate, landfill, advanced oxidation processes, Fenton and Photo-Fenton systems, biological treatment, organic pollutants

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Authors: Mohammed Fakehy, Mohammed Haggag

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The problem of test anxiety considered as one of the most important and most complex psychological problems faced by students of King Saud University, where university students in a need to bring their reassurance and psychological comfort, relieves feeling pain and difficulties of the study. Recently, there are programs and science that help human to change, including the science Linguistic Programming this neural science stems from not just the tips of the need to make the effort or continue to work, but provides the keys in which one can be controlled in the internal environment. Even human potential energy is extracted seeking to achieve success and happiness and excellence. Through the work of the researchers as members of the teaching staff at King Saud University and specialists in the field of psychology noticed the suffering of some students of King Saud University, test anxiety. In an attempt by the researchers to mitigate as much as possible of the unity of this concern, students will have a training program in Neuro Linguistic Programming. The main Question of this study is What is the effectiveness of the impact of a training program using NLP to reduce test anxiety by using a biological feedback. Therefore, the results of this study might serve as a good announcement about the usefulness of NLP programs which influence future research to significant effect of NLP on test anxiety.

Keywords: neuro linguistic programming, test anxiety, biological feedback, king saud

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Authors: Malik SS, Masood N, Mubarik S, Khadim TM

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Introduction: Xeroderma pigmentosum group G (XPG) gene plays a crucial role in the correction of UV-induced DNA damage through nucleotide excision repair pathway. Single nucleotide polymorphisms in XPG gene have been reported to be associated with different cancers. Current case-control study was designed to evaluate the relationship between one of the most frequently found XPG (rs1047768 T>C) polymorphism and breast cancer risk. Methodology: A total of 200 individuals were screened for this polymorphism including 100 pathologically confirmed breast cancer cases and age-matched 100 controls. Genotyping was carried out using Tetra amplification-refractory mutation system (ARMS) PCR and results were confirmed by gel electrophoresis. Results: Conditional logistic regression analysis showed significant association between TC genotype (OR: 8.9, CI: 2.0 – 38.7) and increased breast cancer risk. Although homozygous CC genotype was more frequent in patients as compared to controls, but it was statistically non-significant (OR: 3.9, CI: 0.4 – 35.7). Conclusion: In conclusion, XPG (rs1047768 T>C) polymorphism may contribute towards increased risk of breast cancer but other polymorphisms may also be evaluated to elucidate their role in breast cancer.

Keywords: XPG, breast cancer, NER, ARMS-PCR

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Authors: Arun Kumar, Ravindra Pal Verma, Harsh Sharma, Shani Kumar

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For the present study samples was collected from 20 donors with unknown blood group and secretor status had been determined from saliva by using biological fluid. ABO typing on the concentrated samples was successfully performed after 1 month of storage. Urine stained clothing samples are often submitted to forensic science laboratories for ABH blood group antigen determination. The serogenetic markers of semen stains submitted can be used to determine the origin of any of these samples. ABH blood group substances have previously been identified from urine. ABH blood group substance is low in urine in comparison with other body fluids.

Keywords: ABH blood group, crime scene, serological markers, body fluids and urine

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Authors: Anita Jäger, Andrew Salazar, Jörg von Hagen, Harald Kolmar

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In the treatment of individuals with sensitive and psoriatic skin, several inflammation and itch-related molecular and cellular targets have been identified, but many of these have yet to be characterized. In this study, we present two potential targets in the skin that can be linked to the inflammation and itch cycle. 11ßHSD1 is the enzyme responsible for converting inactive cortisone to active cortisol used to transmit signals downstream. The activation of the receptor NK1R correlates with promoting inflammation and the perception of itch and pain in the skin. In this study, both targets have been investigated based on their involvement in inflammation. The role of both identified targets was characterized based on the secretion of inflammation cytokine- IL6, IL-8, and CCL2, as well as phosphorylation and signaling pathways. It was found that treating skin cells with molecules able to inhibit inflammatory pathways results in the reduction of inflammatory signaling molecules secreted by skin cells and increases their proliferative capacity. Therefore, these molecular targets and their associated pathways show therapeutic potential and can be mitigated via small molecules. This research can be used for further studies in inflammation and itch pathways and can help to treat pathological symptoms.

Keywords: inflammation, itch, signaling pathway, skin

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Authors: Abdol-Hassan Doulah

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In this study, antimicrobial activity of essential oil and ethyl acetate and ether extracts of S. nemorosa were examined against some species of bacteria and fungi. The essential oil of the aerial part of S. nemorosa was examined by GC and GC-MS. In the essential oil of S. nemorosa 26 Compounds have been identified. 2-Nonanone (44.09 %), 2-Undecanone (33.79 %), E-Caryophyllene (3.74 %) and 2-Decanone (2.89 %) were the main components of the essential oil. The essential oil analysis showed greatest antimicrobial activity against Staphylococcus epidermidis (5.3 μg/ml) and S. cerevisiae (9.3 μg/ml). The ethyl acetate showed greatest antimicrobial activity against Bacillus subtilis (106.7 μg/ml), Candida albicans (5.3 μg/ml) and ether extract showed greatest antimicrobial activity against Klebseilla pneumoniae (10.7 μg/ml) and Saccharomyces cerevisiae (10.7 μg/ml). In conclusion, we suggest that the antimicrobial activity of S. nemorosa may be due to its content of germacrene and linalool.

Keywords: antibacterial activity, antifungal activity, Salvia nemorosa L., essential oils, biological activity

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Authors: Soheil Zorofchian Moghadamtousi, Habsah Abdul Kadir, Mohammadjavad Paydar, Elham Rouhollahi, Hamed Karimian

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The present study was designed to evaluate the molecular mechanisms of Annona muricata leaves ethyl acetate extract (AMEAE) against lung cancer A549 cells. Cell viability analysis revealed the selective cytotoxic effect of AMEAE towards A549 cells. Treatment of A549 cells with AMEAE significantly elevated the reactive oxygen species formation, followed by attenuation of mitochondrial membrane potential via upregulation of Bax and downregulation of Bcl-2, accompanied by cytochrome c release to the cytosol. The released cytochrome c triggered the activation of caspase-9 followed by caspase-3. In addition, AMEAE-induced apoptosis was accompanied by cell cycle arrest at G1 phase. Our data showed for the first time that AMEAE inhibited the proliferation of A549 cells, leading to cell cycle arrest and programmed cell death through activation of the mitochondrial-mediated signaling pathway.

Keywords: Annona muricata, lung cancer, apoptosis, mitochondria

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Authors: Jessica Morales Perdomo, Daniel Rodriguez Caicedo, Fernando Cantor Rincon

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Tuta absoluta known as the tomato leaf miner, is one of the main pests in tomato crops in South America and the main pest in many European countries. Apanteles gelechiidivoris is a parasitoid of third instar Tuta absoluta larvae. Our studies have demonstrated that this parasitoid can cause up to 80% mortality of T. absoluta larvae in the field. We investigated cold storage of A. gelechiidivoris pupae as a method of mass production of this parasitoid. This storage method does not interfere with biological characteristics of the parasitoid. In this study, we evaluated the effect of different temperatures (4, 8 and 12°C) and different time duration (7, 14, 21 or 28 days) of cold storage on biological parameters of A. gelechiidivoris pupae and adults. The biological parameters of the parasitoid evaluated were: adult emergence time, lifespan, parasitism percentage and sex ratio. We found that the adult emergence time was delayed when the parasitoid pupae were stored at 4°C and 8°C. The shortest adult emergence was recorded when pupae were stored for seven days. The lowest adult emergence was found for pupae stored at 4°C and decreased significantly as the days of storage increased. We found high percentages of adult emergence when pupae were stored at 8°C and 12°C for seven days. Adult lifespan decreased with increasing days of cold storage. Adults emerging from pupae stored at 8°C during seven and 14 days showed the longest lifespan (nine days). The lowest parasitism rate was recorded at 4°C at every time point. The highest percentage of parasitism (80%) was found at 8°C during seven days of storage. The treatments had no effect on adults the sex ratio. The results suggest that A. gelechiidivoris pupae can be stored for up to 14 days at 8°C without affecting the efficacy of the parasitoid in the field.

Keywords: biological control, cold storage, massive rearing, quality control

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Authors: Christy Rosaline, Rathankar Roa, Waheeta Hopper

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Persistence of tuberculosis, emergence of multidrug-resistance and extensively drug-resistant forms of the disease, has increased the interest in developing new antitubercular drugs. Developing inhibitors for 3-deoxy-D-arabino-heptulosonate 7-phosphate synthase from Mycobacterium tuberculosis (MtbDAH7Ps), an enzyme involved in shikimate pathway, gives a selective target for antitubercular agents. MtbDAH7Ps was screened against ZINC database, and shortlisted compounds were subjected to induce fit docking. Prime/Molecular Mechanics Generalized Born Surface Area calculation was used to validate the binding energy of ligand-protein complex. Molecular Dynamics analysis for of the lead compounds–MtbDAH7Ps complexes showed that the backbone of MtbDAH7Ps in their complexes were stable. These results suggest that the shortlisted lead compounds ZINC04097114, ZINC15163225, ZINC16857013, ZINC06275603, and ZINC05331260 could be developed into novel drug leads to inhibit DAH7Ps in Mycobacterium tuberculosis.

Keywords: MtbDAH7Ps, Mycobacterium tuberculosis, HTVS, molecular dynamics

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Authors: Djeddi Hamssa, Kherief Necereddine Saliha, Mehennaoui Fatima Zohra

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The objectives of this study are to use different parameters to assess the current pollution status of sediments in Rhumel wadi located in the North-East of Algeria (Constantine), two stations were selected in strategic points and sampled at three occasions on Sptember 2014, Junary 2015 and April 2015. Parameters used in this study were a physico-chimical analysis of water (pH, CE, Dissolved O2), sediments (pH, CE, CaCo3, MO) and contamination level of sediments by cadmium, completed by biological testing and analysis of existing benthic community. The results of the physico-chemical parameters show that the water temperature is average and seasonal, the pH value is acidic, does not exceed 6.64. The amplitude variation may be important from upstream to downstream. The generally high electrical conductivity, for the carbonate nature of the watershed increases from upstream to downstream. The waters of the Rhumel wadi are excessively mineralized, dissolved oxygen, a vital factor for benthic community wildlife downstream decreases with increasing organic loading; oxygen is consumed by the microorganisms to its degradation. Analysis of the benthic fauna and calculating the biotic index show a clear excessive pollution for both upstream and downstream stations.

Keywords: biological analysis, benthic fauna, sediments contamination, cadmium

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Authors: Aleksandra Bylinska, Samantha Slight-Webb, Kevin Thomas, Miles Smith, Susan Macwana, Nicolas Dominguez, Eliza Chakravarty, Joan T. Merrill, Judith A. James, Joel M. Guthridge

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Background: Systemic Lupus Erythematosus (SLE) is an interferon-related autoimmune disease characterized by B cell dysfunction. One of the main hallmarks is a loss of tolerance to self-antigens leading to increased levels of autoantibodies against nuclear components (ANAs). However, up to 20% of healthy ANA+ individuals will not develop clinical illness. SLE is more prevalent among women and minority populations (African, Asian American and Hispanics). Moreover, African Americans have a stronger interferon (IFN) signature and develop more severe symptoms. The exact mechanisms involved in ethnicity-dependent B cell dysregulation and the progression of autoimmune disease from ANA+ healthy individuals to clinical disease remains unclear. Methods: Peripheral blood mononuclear cells (PBMCs) from African (AA) and European American (EA) ANA- (n=12), ANA+ (n=12) and SLE (n=12) individuals were assessed by multimodal scRNA-Seq/CITE-Seq methods to examine differential gene signatures in specific B cell subsets. Library preparation was done with a 10X Genomics Chromium according to established protocols and sequenced on Illumina NextSeq. The data were further analyzed for distinct cluster identification and differential gene signatures in the Seurat package in R and pathways analysis was performed using Ingenuity Pathways Analysis (IPA). Results: Comparing all subjects, 14 distinct B cell clusters were identified using a community detection algorithm and visualized with Uniform Manifold Approximation Projection (UMAP). The proportion of each of those clusters varied by disease status and ethnicity. Transitional B cells trended higher in ANA+ healthy individuals, especially in AA. Ribonucleoprotein high population (HNRNPH1 elevated, heterogeneous nuclear ribonucleoprotein, RNP-Hi) of proliferating Naïve B cells were more prevalent in SLE patients, specifically in EA. Interferon-induced protein high population (IFIT-Hi) of Naive B cells are increased in EA ANA- individuals. The proportion of memory B cells and plasma cells clusters tend to be expanded in SLE patients. As anticipated, we observed a higher signature of cytokine-related pathways, especially interferon, in SLE individuals. Pathway analysis among AA individuals revealed an NRF2-mediated Oxidative Stress response signature in the transitional B cell cluster, not seen in EA individuals. TNFR1/2 and Sirtuin Signaling pathway genes were higher in AA IFIT-Hi Naive B cells, whereas they were not detected in EA individuals. Interferon signaling was observed in B cells in both ethnicities. Oxidative phosphorylation was found in age-related B cells (ABCs) for both ethnicities, whereas Death Receptor Signaling was found only in EA patients in these cells. Interferon-related transcription factors were elevated in ABCs and IFIT-Hi Naive B cells in SLE subjects of both ethnicities. Conclusions: ANA+ healthy individuals have altered gene expression pathways in B cells that might drive apoptosis and subsequent clinical autoimmune pathogenesis. Increases in certain regulatory pathways may delay progression to SLE. Further, AA individuals have more elevated activation pathways that may make them more susceptible to SLE.

Keywords:

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Authors: Jasminka Mujic, Karin Milde-Langosch, Volkmar Mueller, Mirza Suljagic, Tea Becirevic, Jozo Coric, Daria Ler

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MACC1 (metastasis associated in colon cancer-1) is a prognostic biomarker for tumor progression, metastasis, and survival of a variety of solid cancers. MACC1 also causes tumor growth in xenograft models and acts as a master regulator of the HGF/MET signaling pathway. In breast cancer, the expression of MACC1 determined by immunohistochemistry was significantly associated with positive lymph node status and advanced clinical stage. The aim of the present study was to further investigate the prognostic or predictive value of MACC1 expression in breast cancer using western blot analysis and immunohistochemistry. The results of our study have shown that high MACC1 expression in breast cancer is associated with shorter disease-free survival, especially in node-negative tumors. The MACC1 might be a suitable biomarker to select patients with a higher probability of recurrence which might benefit from adjuvant chemotherapy. Our results support a biologic role and potentially open the perspective for the use of MACC1 as predictive biomarker for treatment decision in breast cancer patients.

Keywords: breast cancer, biomarker, HGF/MET, MACC1

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Authors: Suresh Kumar Verma, Jugal Kishore Das, Ealisha Jha, Mrutyunjay Suar, SKS Parashar

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In recent years nanoforms of inorganic metallic oxides has attracted a lot of interest due to their small size and significantly improved physical, chemical and biological properties compared to their molecular precursor. Some of the inorganic materials such as TiO2, ZnO, MgO, CaO, Al2O3 have been extensively used in biological applications. Zinc Oxide is a Wurtzite-type semiconductor and piezo-electric material exhibiting excellent electrical, optical and chemical properties with a band energy gap of 3.1-3.4 eV. Nanoforms of Zinc Oxide (ZnO) are increasingly recognised for their utility in biological application. The significant physical parameters such as surface area, particle size, surface charge and Zeta potential of Zinc Oxide (ZnO) nanoparticles makes it suitable for the uptake, persistance, biological, and chemical activities inside the living cells. The present study shows the effect of intrinsic defects of ZnO nanocrystals synthesized by high energy ball milling (HEBM) technique in their antibacterial activities. Bulk Zinc oxide purchased from market were ball milled for 7 h, 10 h, and 15 h respectively to produce nanosized Zinc Oxide. The structural and optical modification of such synthesized particles were determined by X-ray diffraction (XRD), Scanning Electron Microscopy and Electron Paramagnetic Resonance (EPR). The antibacterial property of synthesized Zinc Oxide nanoparticles was tested using well diffusion, minimum inhibitory Concentration, minimum bacteriocidal concentration, reactive oxygen species (ROS) estimation and membrane potential determination methods. In this study we observed that antibacterial activity of ZnO nanoparticles is because of the intrinsic defects that exist as a function of difference in size and milling time.

Keywords: high energy ball milling, ZnO nanoparticles, EPR, Antibacterial properties

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Authors: Bounoua Nadia, Rebizi Mohamed Nadjib

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Chiral molecules in relation to particular biological roles are stereoselective. Enantiomers differ significantly in their biochemical responses in a biological environment. Despite the current advancement in drug discovery and pharmaceutical biotechnology, the chiral separation of some racemic mixtures continues to be one of the greatest challenges because the available techniques are too costly and time-consuming for the assessment of therapeutic drugs in the early stages of development worldwide. Various nanoparticles became one of the most investigated and explored nanotechnology-derived nanostructures, especially in chirality, where several studies are reported to improve the enantiomeric separation of different racemic mixtures. The production of surface-modified nanoparticles has contributed to these limitations in terms of sensitivity, accuracy, and enantioselectivity that can be optimized and therefore makes these surface-modified nanoparticles convenient for enantiomeric identification and separation.

Keywords: chirality, enantiomeric recognition, selectors, analysis, surface-modified nanoparticles

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Authors: Mohammad Reza Hossein Zadeh

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Plants have different layers of defense responses against biotic and abiotic stresses. One of the well-defined defense mechanism in plants is systemic acquired resistance (SAR) against a broad-range of pathogens. Salicylic acid (SA) plays a crucial role in regulation of the SAR pathway. It has been proved that Chemically SA-like compounds can mimic the SA signaling role. Imidocloprid is an insecticide being used to control whiteflies on crop plants. In order to study the possible role of Imidocloprid as an elicitor of SAR in plants, experiments were conducted in a completely randomized design frame with three treatments and duplicates on the detached leaves and whole Nicotiana tabacum var. Samsun NN. plants inoculated with Tobacco mild green mosaic virus (TMGMV). Compared with the effect of other SAR-inducers such as SA, Imidoclorid conferred a robust SAR induction in the infected plants. The results suggested that Imidocloprid even more powerful than SA can be considered as strong SAR inducer in the infected plants with viruses, which develop the local lesion symptoms.

Keywords: imidocloprid, Nicotiana tabacum var. Samsun NN, SAR, tobacco mild green, mosaic virus

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Authors: Mustapha Mahmoud, Fouzia Toumi Benali, Mohamed Benyahia, Sofiane Bouazza

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This work focuses on the influences of biological and chemical parameters on the phenolic compounds such as flavonoids and tannins in different medicinal plants in western Algeria (Papaver rhoeas, Daphnegnidium, Lavandula multifida, Lavandula dentata, Lavandula stoicha, ...). Thus we look the difference between species of the same genus, difference between the different organs of the same species, the influence of environment all temperature influences, time, percentage of solvent on the extraction. Quantification of the phenolic compounds was performed by spectrophotometric method then treated with statistics tools such as variance analysis, multivariant analyzes, response surface methodology). The results show that the polyphenols are influenced by the parameters mentioned.

Keywords: polyphenols, influences, medicinal plants, west Algeria

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Authors: Nouf A. Aldarmahi, Nesrin I. Tarbiah, Nuha A. Alkhattabi, Huda F. Alshaibi

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Nigella sativa which is known as dark cumin is a well-known example for a widely applicable herbal medicine. Nigella sativa can be effective in a variety of diseases such as hypertension, diabetes, bronchitis, gastrointestinal upset, and cancer. The anticancer effect of Nigella sativa appeared to be mediated by immune-modulatory effect through stimulating human natural killer (NK) cells. This is a type of lymphocytes which is part of the innate immunity, also known as the first line of defense in the body against pathogens. This study investigated the effect of thymoquinone as a major component of Nigella sativa on the molecular cytotoxic pathway of NK cell and the role of thymoquinone therapeutic effect on NK cells. NK cells were cultured with breast tumor cells in different ways and cultured media was collected and the concentration of perforin, granzyme B and interferon-α were measured by ELISA. The cytotoxic effect of NK cells on breast tumor cells was enhanced in the presence of thymoquinone, with increased activity of perforin in NK cells. This improved anticancer effect of thymoquinone on breast cancer cells.

Keywords: breast cancer, cancer cells, natural killer cells, thymoquinone

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Authors: Paul Shize Li, Frank Alber

Abstract:

A fundamental task of clinical genomics is to unravel the functions of genes and their associations with disorders. Although experimental biology has made efforts to discover and elucidate the molecular mechanisms of individual genes in the past decades, still about 40% of human genes have unknown functions, not to mention the diseases they may be related to. For those biologists who are interested in a particular gene with unknown functions, a powerful computational method tailored for inferring the functions and disease relevance of uncharacterized genes is strongly needed. Studies have shown that genes strongly linked to each other in multiple biological networks are more likely to have similar functions. This indicates that the densely connected subgraphs in multiple biological networks are useful in the functional and phenotypic annotation of uncharacterized genes. Therefore, in this work, we have developed an integrative network approach to identify the frequent local clusters, which are defined as those densely connected subgraphs that frequently occur in multiple biological networks and consist of the query gene that has few or no disease or function annotations. This is a local clustering algorithm that models multiple biological networks sharing the same gene set as a three-dimensional matrix, the so-called tensor, and employs the tensor-based optimization method to efficiently find the frequent local clusters. Specifically, massive public gene expression data sets that comprehensively cover dynamic, physiological, and environmental conditions are used to generate hundreds of gene co-expression networks. By integrating these gene co-expression networks, for a given uncharacterized gene that is of biologist’s interest, the proposed method can be applied to identify the frequent local clusters that consist of this uncharacterized gene. Finally, those frequent local clusters are used for function and disease annotation of this uncharacterized gene. This local tensor clustering algorithm outperformed the competing tensor-based algorithm in both module discovery and running time. We also demonstrated the use of the proposed method on real data of hundreds of gene co-expression data and showed that it can comprehensively characterize the query gene. Therefore, this study provides a new tool for annotating the uncharacterized genes and has great potential to assist clinical genomic diagnostics.

Keywords: local tensor clustering, query gene, gene co-expression network, gene annotation

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Authors: Adenike Adesanya, Nonthaphat Wong, Xiang-Yun Lan, Shea Ping Yip, Chien-Ling Huang

Abstract:

Background: The most challenging mutation of the oncokinase BCR-ABL protein T315I, which is commonly known as the “gatekeeper” mutation and is notorious for its strong resistance to almost all tyrosine kinase inhibitors (TKIs), especially imatinib. Therefore, this study aims to identify T315I-dependent downstream microRNA (miRNA) pathways associated with drug resistance in chronic myeloid leukemia (CML) for prognostic and therapeutic purposes. Methods: T315I-carrying K562 cell clones (K562-T315I) were generated by the CRISPR-Cas9 system. Imatinib-treated K562-T315I cells were subjected to small RNA library preparation and next-generation sequencing. Putative lncRNA-miRNA-mRNA networks were analyzed with (i) DESeq2 to extract differentially expressed miRNAs, using Padj value of 0.05 as cut-off, (ii) STarMir to obtain potential miRNA response element (MRE) binding sites of selected miRNAs on lncRNA H19, (iii) miRDB, miRTarbase, and TargetScan to predict mRNA targets of selected miRNAs, (iv) IntaRNA to obtain putative interactions between H19 and the predicted mRNAs, (v) Cytoscape to visualize putative networks, and (vi) several pathway analysis platforms – Enrichr, PANTHER and ShinyGO for pathway enrichment analysis. Moreover, mitochondria isolation and transcript quantification were adopted to determine the new mechanism involved in T315I-mediated resistance of CML treatment. Results: Verification of the CRISPR-mediated mutagenesis with digital droplet PCR detected the mutation abundance of ≥80%. Further validation showed the viability of ≥90% by cell viability assay, and intense phosphorylated CRKL protein band being detected with no observable change for BCR-ABL and c-ABL protein expressions by Western blot. As reported by several investigations into hematological malignancies, we determined a 7-fold increase of H19 expression in K562-T315I cells. After imatinib treatment, a 9-fold increment was observed. DESeq2 revealed 171 miRNAs were differentially expressed K562-T315I, 112 out of these miRNAs were identified to have MRE binding regions on H19, and 26 out of the 112 miRNAs were significantly downregulated. Adopting the seed-sequence analysis of these identified miRNAs, we obtained 167 mRNAs. 6 hub miRNAs (hsa-let-7b-5p, hsa-let-7e-5p, hsa-miR-125a-5p, hsa-miR-129-5p, and hsa-miR-372-3p) and 25 predicted genes were identified after constructing hub miRNA-target gene network. These targets demonstrated putative interactions with H19 lncRNA and were mostly enriched in pathways related to cell proliferation, senescence, gene silencing, and pluripotency of stem cells. Further experimental findings have also shown the up-regulation of mitochondrial transcript and lncRNA MALAT1 contributing to the lncRNA-miRNA-mRNA networks induced by BCR-ABL T315I mutation. Conclusions: Our results have indicated that lncRNA-miRNA regulators play a crucial role not only in leukemogenesis but also in drug resistance, considering the significant dysregulation and interactions in the K562-T315I cell model generated by CRISPR-Cas9. In silico analysis has further shown that lncRNAs H19 and MALAT1 bear several complementary miRNA sites. This implies that they could serve as a sponge, hence sequestering the activity of the target miRNAs.

Keywords: chronic myeloid leukemia, imatinib resistance, lncRNA-miRNA-mRNA, T315I mutation

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Authors: Kun-Ting Song, Christian Schott, Peter Schneider, Sebastian Watzele, Regina Kluge, Elena Gubanova, Aliaksandr S. Bandarenka

Abstract:

The combination of electrochemical impedance spectroscopy (EIS) and the hydrodynamic technique like rotation disc electrode (RDE) provides a critical method for quantitively investigating mechanisms of hydrogen evolution reaction (HER) in acidic and alkaline media. Pt5Gd represented higher HER activities than polycrystalline Pt (Pt(pc)) by means of the surface strain effects. The model of the equivalent electric circuit to fit the impedance data under the RDE configurations is developed. To investigate the relative reaction contribution, the ratio of the charge transfer reactions of the Volmer-Heyrovsky and Volmer-Tafel pathways on Pt and Pt5Gd electrodes is determined. The ratio remains comparably similar in acidic media, but it changes in alkaline media with Volmer–Heyrovsky pathway dominating. This combined approach of EIS and RDE can help to study the electrolyte effects and other essential reactions for electrocatalysis in future work.

Keywords: hydrogen evolution reaction, electrochemical impedance spectroscopy, hydrodynamic methods, electrocatalysis, electrochemical interface

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Authors: Benbelkacem Ouerdia

Abstract:

Heterotrophic denitrification has been proven to be one of the most feasible processes for removing nitrate from wastewater and drinking water. In this process, heterotrophic bacteria use organic carbon for both growth and as an electron source. Underground water pollution by nitrates become alarming in Algeria. A survey carried out revealed that the nitrate concentration is in continual increase. Studies in some region revealed contamination exceeding the recommended permissible dose which is 50 mg/L. Worrying values in the regions of Mascara, Ouled saber, El Eulma, Bouira and Algiers are respectively 72 mg/L, 75 mg/L, 97 mg/L, 102 mg/L, and 158 mg/L. High concentration of nitrate in drinking water is associated with serious health risks. Research on nitrate removal technologies from municipal water supplies is increasing because of nitrate contamination. Biological denitrification enables the transformation of oxidized nitrogen compounds by a wide spectrum of heterotrophic bacteria into harmless nitrogen gas with accompanying carbon removal. Globally, denitrification is commonly employed in biological nitrogen removal processes to enhance water quality The study investigated the valorization of a vegetable residue as a carbon source (dates nodes) in water treatment using the denitrification process. Throughout the study, the effect of inoculums addition, pH, and initial concentration of nitrates was also investigated. In this research, a natural organic substance: dates nodes were investigated as a carbon source in the biological denitrification of drinking water. This material acts as a solid substrate and bio-film carrier. The experiments were carried out in batch processes. Complete denitrification was achieved varied between 80 and 100% according to the type of process used. It was found that the nitrate removal rate based on our results, we concluded that the removal of organic matter and nitrogen compounds depended mainly on the initial concentration of nitrate. The effluent pH was mainly affected by the C/N ratio, where a decrease increases pH.

Keywords: biofilm, carbon source, dates nodes, heterotrophic denitrification, nitrate, nitrite

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Authors: Sami El Khatib, Agnès Leroux, Jean-Louis Merlin, François Guillemin, Marie-Ange D’Hallewin

Abstract:

Photodynamic therapy (PDT) is a treatment modality based on the cytotoxic effect occurring on the target tissues by interaction of a photosensitizer with light in the presence of oxygen. One of the major advances in PDT can be attributed to the use of topical aminolevulinic (ALA) to induce Protoporphyrin IX (PpIX) for the treatment of early stage cancers as well as diagnosis. ALA is a precursor of the heme synthesis pathway. Locally delivered to the target tissue ALA overcomes the negative feedback exerted by heme and promotes the transient formation of PpIX in situ to reach critical effective levels in cells and tissue. Whereas early steps of the heme pathway occur in the cytosol, PpIX synthesis is shown to be held in the mitochondrial membranes and PpIX fluorescence is expected to accumulate in close vicinity of the initial building site and to progressively diffuse to the neighboring cytoplasmic compartment or other lipophylic organelles. PpIX is known to be highly reactive and will be degraded when irradiated with light. PpIX photobleaching is believed to be governed by a singlet oxygen mediated mechanism in the presence of oxidized amino acids and proteins. PpIX photobleaching and subsequent spectral phototransformation were described widely in tumor cells incubated in vitro with ALA solution, or ex vivo in human and porcine mucosa superfused with hexylaminolevulinate (hALA). PpIX photobleaching was also studied in vivo, using animal models such as normal or tumor mice skin and orthotopic rat bladder model. Hexyl aminolevulinate a more potent lipophilic derivative of ALA was proposed as an adjunct to standard cystoscopy in the fluorescence diagnosis of bladder cancer and other malignancies. We have previously reported the effectiveness of hALA mediated PDT of rat bladder cancer. Although normal and tumor bladder epithelium exhibit similar fluorescence intensities after intravesical instillation of two hALA concentrations (8 and 16 mM), the therapeutic response at 8mM and 20J/cm2 was completely different from the one observed at 16mM irradiated with the same light dose. Where the tumor is destroyed, leaving the underlying submucosa and muscle intact after an 8 mM instillation, 16mM sensitization and subsequent illumination results in the complete destruction of the underlying bladder wall but leaves the tumor undamaged. The object of the current study is to try to unravel the underlying mechanism for this apparent contradiction. PpIX extraction showed identical amounts of photosensitizer in tumor bearing bladders at both concentrations. Photobleaching experiments revealed mono-exponential decay curves in both situations but with a two times faster decay constant in case of 16mM bladders. Fluorescence microscopy shows an identical fluorescence pattern for normal bladders at both concentrations and tumor bladders at 8mM with bright spots. Tumor bladders at 16 mM exhibit a more diffuse cytoplasmic fluorescence distribution. The different response to PDT with regard to the initial pro-drug concentration can thus be attributed to the different cellular localization.

Keywords: bladder cancer, hexyl-aminolevulinate, photobleaching, confocal fluorescence microscopy

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